Strategies to resolve the gap in adolescent tuberculosis care at four health facilities in Uganda: The teenager’s TB pilot project

In 2021, an estimated 10.6 million people fell ill with tuberculosis (TB) globally and 11.3% were children. About 40% of children aged five to fourteen years with TB are missed annually. In Uganda, 44% of adolescents with chronic cough of more than two weeks do not seek care from health facilities. Therefore, strategies to promote health care-seeking behaviour among adolescents were urgently needed to resolve the gap. In regard to this, the research project utilized a before and after design, in which the number of adolescents (10-19years) enrolled in the project health facilities were compared before and after the intervention. The intervention package that comprised of tuberculosis awareness and screening information was developed together with adolescents, thus; a human-centred approach was used. The package consisted of TB screening cards, poster messages and a local song. The song was broadcasted in the community radios. Poster messages were deployed in the community by the village health teams (VHTS). The TB screening cards were given to TB positive and presumptive adults to screen adolescents at home. Adolescents that were found with TB symptoms were referred to the project health facilities. Socio-demographic and clinical characteristics of eligible adolescents were collected in a period of six months from Kawolo, Iganga, Gombe and Kiwoko health facilities. To determine the effectiveness of the package, before and after intervention data were equally collected. A total of 394 adolescents were enrolled, majority (76%) were school going. The intervention improved adolescent TB care seeking in the four project health facilities. The average number of adolescents screened increased from 159 to 309 (incidence rate ratio (IRR) = 1.9, P<0.001, 95% CI [1.9, 2.0]). Those presumed to have TB increased from 13 to 29(IRR = 2.2, P<0.001, 95% CI [1.9, 2.5]). The ones tested with GeneXpert increased in average from 8 to 28(IRR = 3.3, P<0.001, 95% CI [2.8, 3.8]). There was a minimal increase in the average monthly number of adolescents with a positive result of 0.8, from 1.6 to 2.4(p = 0.170) and linkage to TB care services of 1.1, from 2 to 3.1(p = 0.154). The project improved uptake of TB services among adolescents along the TB care cascade. We recommend a robust and fully powered randomized controlled trial to evaluate the effectiveness of the Package.


Introduction
In 2021, an estimated 10.6 million people fell ill with tuberculosis (TB) globally, 1.2 million of these were children.About 40% of them aged between 5 and 14 years with TB are missed annually.In Uganda, 44% of adolescents with chronic cough of ≥2 weeks do not seek care from health facilities.Therefore, strategies to promote health care-seeking behaviour among adolescents are urgently needed.We piloted a project (TEEN TB project) aimed at improving uptake of tuberculosis (TB) care services among adolescents at Ugandan health facilities.Methodology We developed an adolescent TB awareness and screening package using the human centred design.This technique puts real people at the centre of the development process.The package consisted of 3 interventions (TB screening cards, adolescent-TB awareness poster messages and a local TB awareness song) deployed in the project health facilities and their surrounding communities.Data on socio-demographic and clinical characteristics of adolescents were collected for the period between October 2021 and March 2022 at 4 project health facilities (Kawolo, Iganga, Gombe and Kiwoko).We collected before and after intervention data from facility level records to determine the effect of the package.Results A total of 394 adolescents were included and the majority (76%) were still in school.Overall, the intervention improved adolescent TB care in the four project health facilities.The average number of adolescents screened increased by 94% from 159 to 309, with an incidence rate ratio (IRR) of 1.9 ( 95% CI: 1.9-2.0,p <0.001), there was a 2-fold increase among those presumed to have TB; from 13 to 29, IRR of 2.2 (95% CI: 1.9-2.5, p <0.001) and those tested with GeneX-pert and microscopy increased more than 3 times from 8 to 28, IRR of 3.3 ( 95% CI: 2.8-3.8,p <0.001).There was a minimal increase in the average monthly number of adolescents with a positive result from 1.6 to 2.4 and linkage to TB care services from 2 to 3.1.These were not statistically significant at p=0.170 and p=0.154 respectively.

Conclusion
The project improved uptake of TB services among adolescents along the TB care cascade (screening, TB testing and linkage to care).We recommend a robust and fully powered randomized controlled trial to evaluate the effectiveness of the package.The data underlying the results presented in the study are available from (include the name of the third party and contact information or URL).This text is appropriate if the data are owned by a third party and authors do not have permission to share the data.

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Introduction
In 2021, an estimated 10.6 million people fell ill with tuberculosis (TB) globally, 1.2 million of these were children.About 40% of them aged between 5 and 14 years with TB are missed annually.In Uganda, 44% of adolescents with chronic cough of ≥2 weeks do not seek care from health facilities.Therefore, strategies to promote health care-seeking behaviour among adolescents are urgently needed.We piloted a project (TEEN TB project) aimed at improving uptake of tuberculosis (TB) care services among adolescents at Ugandan health facilities.

Methodology
We developed an adolescent TB awareness and screening package using the human centred design.This technique puts real people at the centre of the development process.The package consisted of 3 interventions (TB screening cards, adolescent-TB awareness poster messages and a local TB awareness song) deployed in the project health facilities and their surrounding communities.Data on socio-demographic and clinical characteristics of adolescents were collected for the period between October 2021 and March 2022 at 4 project health facilities (Kawolo, Iganga, Gombe and Kiwoko).We collected before and after intervention data from facility level records to determine the effect of the package.

Results
A total of 394 adolescents were included and the majority (76%) were still in school.Overall, the intervention improved adolescent TB care in the four project health facilities.The average number of adolescents screened increased by 94% from 159 to 309, with an incidence rate ratio (IRR) of 1.9 ( 95% CI: 1.9-2.0,p <0.001), there was a 2-fold increase among those presumed to have TB; from 13 to 29, IRR of 2.2 (95% CI: 1.9-2.5, p <0.001) and those tested with GeneX-pert and microscopy increased more than 3 times from 8 to 28, IRR of 3.3 ( 95% CI: 2.8-3.8,p <0.001).There was a minimal increase in the average monthly number of adolescents with a positive result from 1.6 to 2.4 and linkage to TB care services from 2 to 3.1.These were not statistically significant at p=0.170 and p=0.154 respectively.

Conclusion
The project improved uptake of TB services among adolescents along the TB care cascade (screening, TB testing and linkage to care).We recommend a robust and fully powered randomized controlled trial to evaluate the effectiveness of the package.

Keywords: Tuberculosis, awareness package, Intervention, Adolescents Introduction
Globally, an estimated 10.6 million people fell ill with tuberculosis (TB) in 2021; among these 1.2 million were children 1 .Previous, in 2020 the incidence of TB was 220 TB cases per 100, 000 populations in Africa 2 .In the same year, a total case notification of 1.4 million with TB treatment coverage of 56%, and a TB case fatality ratio of 22% was reported 2 .In Uganda, TB incidence stands at 196 cases per 100,000 populations, treatment coverage at 68%, case fatality ratio at 19%, with 62,526 cases notified 2 .Globally, 36% of TB cases are missed in health centres, and these are either undiagnosed or unreported 3 .The prevalence to notification ratio stands at 1.7.Globally, about 40% of TB cases among children aged between 5 and 14 years are missed annually 4 .There is currently no routine reporting of TB data among adolescents (10-19 years).Additionally, there is paucity of epidemiological data to guide interventions that address the specific needs of adolescents 5 .One of the barriers to TB case finding in adolescents is low rates of TB screening and testing in this age group, as demonstrated in the Uganda National TB survey which revealed that only 56% of adolescents reporting a chronic cough of ≥2 weeks sought care from health facilities.Only 3% of these were asked to provide sputum and 1.8% were asked to undergo a chest X-ray (CXR) examination 6 .Although there are several other reasons for the low TB testing in adolescents, lack of skills and knowledge by the health care workers to deliver adolescent friendly health services are some of the leading barriers 7 .Studies have revealed that delays in diagnosis, stigma related with diagnosis and treatment, long waiting hours at health facilities, absence of nutritional support for patients with TB, and absence of comprehensive psychosocial support programs are barriers to access and adherence to TB care 7,8 .Strategies including community engagement, training health workers and strengthening public-private partnerships have been found vital in TB control and reducing the missed cases 9 .Strategies to promote care-seeking behaviours among adolescents (demand creation) and ensuring adequate evaluation in health facilities are needed to bridge the gap in the quality of TB care among adolescents.In response to this, we piloted an adolescent TB care package at four health facilities aimed at improving adolescent TB care seeking behaviour.

Project design
A human centred design was used to develop the adolescent-friendly TB awareness and screening package.The package comprised of adolescent TB educative and informative messages simulated in form of educational posters, TB awareness local song ("Bulamu bwo") and TB screening cards.This package was implemented in four (4) project health facilities.
Implementation phase had a number of activities that were kick started by a meeting with The health workers and volunteers oriented the adults who sought care in the TB clinics or with TB symptoms and had adolescents at home on filling of the TB-screening cards.These adults were eventually given the cards to screen their adolescents at home, they were asked to send adolescents found with TB symptoms to the project health facilities to seek care.Poster messages and screening cards were implemented for six (6) months (October, 2021 to March, 2022).The local song was played on the radio stations for 3 months (January to March 2022).
Adolescents who reported to the health facility from October 2021 to March 2022 were subjected to TB screening; those who presented with any of the four symptoms (cough, fever, drenching night sweats and weight loss) were consented (≥ 18years), or assented (< 18 years) and enrolled into the project.These adolescents were taken through the entire TB care cascade (screening, testing and linkage).All responses on socio-demographic and clinical characteristics of the enrolled adolescents were captured into a computer tablet.This data was retrieved and analyzed.To assess the impact of the package, before and after intervention data for adolescents screened, presumptive, GeneXpert tested, positive for TB and those linked to TB care was collected from the health facility registers and analyzed.

Project settings
The study sites included health centers and district level hospitals that were randomly selected.These were health facilities with TB diagnostic and treatment units located in both rural and urban places in the central region of Uganda.Among the four health facilities selected, Kiwoko and Gombe hospitals were rural, while Iganga and Kawolo hospitals were urban.Gombe is a public health facility with 100 bed capacity, while Kiwoko is a faithbased private health facility with 204 bed capacity.The other two facilities (Iganga and Kawolo hospitals) are both public urban health facilities with up to 100 bed capacity.All the health facilities offer TB and other services, such as out-patients, in-patients, antenatal, HIV, eye, dental, nutrition and community services.

Project participants
The project participants included adolescents who presented to the health facilities at different service delivery points such as outpatient department, HIV/ART clinic, maternal and reproductive health clinic (MRH), inpatient wards and TB clinics.We included all adolescents aged 10-19 years with at least one symptom suggestive of TB; predefined according to the World Health Organisation's (WHO) criteria (cough for ≥2 weeks; persistent fever for ≥2 weeks; noticeable weight loss; and excessive night sweats).TB patients who were already on TB treatment or had been screened within two weeks were excluded.

Data collection
Adolescents (10-19 years) who came to the project health facilities were identified from the service delivery points (OPD, ART clinic, MRH clinic, TB clinic and wards) and screened for TB using the national screening algorithm.Those with at least one of the TB symptoms and not on anti-TB treatment were considered eligible and were consented (≥ 18years) or assented (≤ 18 years) by their parents or health workers and enrolled into the project.
Identification numbers were provided and electronic interviewer-administered structured questionnaires were used to collect data from each of the adolescents who participated in the project.All the enrolled adolescents were subjected to TB testing using either GeneXpert or smear microscopy.Those who tested TB positive were initiated on treatment, while the negative ones were treated as per the TB national guidelines.

Data management/analysis
Socio-demographics and clinical characteristics data were collected from the adolescents.
Aggregate level data was collected from health facility registers for different variables such as number screened, number presumed and number tested.This data was collected 6 months before and after the intervention.

Socio-demographic characteristics
Data on socio-demographics was collected during the intervention phase to assess the response to the implemented package in-terms of the different characteristics.
Majority, 336(85%) were unmarried.Kawolo hospital enrolled the highest number, 137(35%) of adolescents compared to the other health facilities as shown in table 1 bellow.

Impact of package on TB care cascade
The impact of the package on adolescent TB care is presented along the TB care cascade In Figure 1, 2, Tables 3, 4 and 5.
The entire analysis revealed the following results:

Screening for TB
There was an increase in the numbers of adolescents screened for TB after the intervention across all the four project health facilities.The overall average increase was 94% (159 to 309).This increase resulted in 1.9 incident rate ratio (IRR) at 95% CI: 1.9-2.0 and this was statistically significant (p <0.001).Iganga hospital had a threefold increase in the number screened from 213 to 629.The increase gave rise to 3.0 IRR at 95% CI: 2.8-3.2 and was statistically significant (p < 0.001).Kawolo hospital had 45% (185 to 269) resulting in 1.5 IRR at 95% CI: 1.4-1.6.This increase was statistically significant (p < 0.001).Kiwoko Hospital had 80% (15-27) resulting in 1.8 IRR at 95% CI: 1.4-2.4 the increase was statistically significant (p <0.001) and Gombe hospital 38% (224 to 309), giving rise to 1.4 IRR at 95% CI: 1.3-1.5, and was statistically significant (p <0.001).The details of numbers screened before and after the intervention are indicated in Figures 1 and 2 and Table 3.

TB Presumptive patients
There was an increase in the average number of presumptive TB adolescents identified during the project period.The overall average increase after the intervention was from 13 to 29, thus, more than double the number before.This resulted in 2.2 incident rate ration (IRR) at 95% CI, 1.9-2.5 that was statistically significant (p <0.001).Iganga hospital had more than double increase from 19 to 44.The increase gave rise to an IRR of 2.3 at 95% CI: 1.9 -2.9, and this was statistically significant (p < 0.001).Kawolo hospital had a threefold increase from 18 to 53 resulting in an IRR of 2.9 at 95% CI: 2.3 -3.6, this was statistically significant (p < 0.001).Kiwoko hospital had 50% (4 to 6) resulting in an IRR of 1.6 at 95% CI: 0.9-5.4,an increase that was not statistically significant (p= 0.105) and Gombe hospital had 17% (12 to 14), giving rise to an IRR of 1.1 at 95% CI: 0.8-1.6,this was not statistically significant (p=0.467).The details of the presumptive TB before and after the intervention are indicated in Figures 1and 2 and Table 4.

TB testing
The overall average number of adolescents tested for TB increased from 8 to 28 after the intervention, this was more than threefold increase resulting in an IRR of 3.3 at 95% CI: 2.8-3.8.This increase was statistically significant (p <0.001).The increase was more than sixfold in Iganga hospital from 7 to 42 resulting in an IRR of 6.5 at 95% CI: 4.6-9.1 which was statistically significant (p <0.001).Kawolo hospital had a threefold increase from 18 to 53 resulting in an IRR of 2.9 at 95% CI: 2.3-3.6, which was statistically significant (p <0.001).

TB Positive adolescents
Overall, there was minimal average increase in the number of TB positive adolescents identified after the intervention by 50% (2 to 3), and this was not statistically significant (p=0.170).An increase of 60% (5 to 8) was registered in Iganga hospital, 25% (4 to 5) in Gombe hospital while Kawolo hospital had an increase of 24% (67 to 83).Kiwoko hospital registered a reduction by-16% (0.83 to 0.67) as indicated in Figures 1 and 2.

Linkage to TB care and treatment
There was minimal improvement in linkage of adolescents to treatment and care, there was 50% (2 to 3.1) increase in the number linked after the intervention, though not statistically significant (p=0.154).Gombe hospital had more than two-fold increase from 67 to 170, Iganga hospital had 50% increase (6 to 9), Kawolo hospital had an increase of 24% (67 to 83).Kiwoko hospital registered a decline at -16% (83 to 67) as shown in Figures 1 and 2.

Discussion
The project sought to resolve the gap in adolescent TB care seeking behavior using a human centered design approach.An adolescent TB awareness and screening package was developed and piloted in four health facilities in central Uganda.Generally findings indicated a statistically significant increase in the number of adolescents screened, TB presumptive and those tested for TB.This significant increase was a result of broadening strategies to disseminate TB information to sensitize adolescents to seek care.One of the studies on adolescent TB had a similar argument by suggesting a comprehensive response to adolescent TB 10 Female adolescents participated more in this study as compared to males, a trend that has been demonstrated by many other adolescent studies, with the high number of females registered being associated with their high susceptibility to TB as compared to their male counterparts 11. .Majority of the TB positives were students.This similar finding was realised in a study that was done in Swaziland schools that captured many TB positive cases from students at schools 12. .Many presumptive cases reported family contacts.Close contact mixing is a common phenomenon demonstrated by a number of studies, for instance the age-and sexspecific social contact study done in the Zambian and South African communities that revealed more than 50% of infections in children resulting from contacts with adult men 13 .
Majority of the enrolled adolescent had no history of smoking or alcohol consumption.
Cigarette smoking and alcohol consumption in this case were considered as minimal risk factors for adolescent TB, contrary to this finding, however, some studies have shown close association between TB and cigarette smoking /alcohol consumption 14 .
While sputum was the main sample used for TB detection as per WHO recommendations on adolescent TB testing, a few x-rays were as well done.These findings related to the 2015 Ugandan TB survey where 1.8% of the participants had X-rays done and 3% of participants asked to provide sputum samples 6,15 Among the key TB awareness interventional approaches that were implemented to close the gap in adolescent TB care seeking, the local song ("Bulamu bwo") played on radio stations sensitized more adolescents to seek care as compared to TB adolescent poster messages and TB screening done at house hold level by parents or caregivers.Just like this project utilized an awareness strategy, a study in Bangladesh similarly emphasised on increased awareness and service delivery by health care workers as promoters and motivators of increased health care seeking behaviour 16 Besides the three key intervention approaches, many received information about TB from the research teams in the health facilities, community village health teams (VHTs) and social media.Apart from lack of information, other similar studies have also documented stigma, delays in diagnosis, long waiting hours, absence of nutritional support and psychosocial support as related factors associated with poor TB health care seeking 8 , 17 Screening done by parents or guardians at household level demonstrated a potential community approach to reach and mobilize adolescents to seek care.This kind of intervention is a way to enhance contact tracing, which many studies have documented as an approach to easily reach and mobilize TB presumptive patients for testing , 18 Most of the adolescents that were enrolled into the project had prior knowledge on TB and had ever heard about adolescent TB, this was an encouraging finding given that other studies have shown lack of knowledge as a leading barrier to TB health care seeking 19 Before and after project implementation data obtained from the health facility registers demonstrated a positive impact on numbers screened, presumptives and those tested using GeneXpert.However, this project registered minimal numbers of adolescents who tested positive for TB and linked to care.Despite the minimal numbers, more TB positives were registered in urban project health facilities that had more reliable stations that played the local song as compared to the rural health This kind of finding was similarly shown in a study done on the burden of adolescent TB in rural eastern Uganda in which a low incident rate was registered 20

Conclusion
The intervention generally improved adolescent TB care seeking behavior along all the important steps of the TB care cascade (screening, TB testing, TB positives and linkage to care).The use of human centered design that directly involved the adolescents in preparing the interventions was a real strength for the project success.However, being a pilot project implemented at the health facilities, we were not able to reach out to other adolescent communities such as schools and distant villages.These results are unlikely to be generalizable.Secondly, our study depended on self-reported responses, which could be affected by recall bias.Out of the many intervention methods that were provided by the expert designers, we were able to only implement three (3) of them due to COVID-19 restrictions, hence impacting on the number of adolescents reached.Additionally, it was not possible to come up with appropriate comparisons of the three interventions because they were not implemented at the same time, although conclusions were drawn after harmonizing the intervention periods.
Given the above said limitations, tthere is a great need to devise mechanisms to mobilize adolescents to seek TB care.Since this was a pilot project, we recommend a robust and fully powered randomized controlled trial to mobilize more adolescents and more so evaluate the effectiveness of the package.
with the following details: Initials of the authors who received each award • Grant numbers awarded to each author • The full name of each funder • URL of each funder website • Did the sponsors or funders play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript?• NO -Include this sentence at the end of your statement: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptbelow to enter a competing interest statement for this submission.On behalf of all authors, disclose any competing interests that could be perceived to bias this work-acknowledging all financial support and any other relevant financial or nonfinancial competing interests.
relevant stakeholders (Ministry of Health, educational and political leaders, and key adolescent health care providers).The meeting was led by the National TB programme with the research team providing technical support.During this meeting, the project team presented data on the clinical and economic burden and unmet needs of TB among adolescents.Besides engagement of different stakeholders, health workers were given three (3) days training by TB programme staff, assisted by the research team.The training focused on Four (4) key ingredients of adolescent friendly health services such as; being nonjudgmental, friendly adolescent services, service demand creation and community awareness/ support.Implementation of TB awareness package was done through the support of project volunteers, research assistants, village health teams (VHTs) and health workers.The VHTs displayed posters on collection points of adolescents in the communities, in the project health facilities and drug shops/stores to sensitize adolescents to seek TB care.The VHTs also identified and engaged local radios serving respective communities to play the local song.

Figure 1 .
Figure 1.Bar graphs showing the before & after intervention average monthly scores of

Figure 2 .
Figure 2. Bar graph showing the overall six months average scores for adolescents screened, The data was cleaned with Microsoft Excel program version 2016 and analyzed with STATA version 14 software.Descriptive univariate analysis was conducted to get the averages per facility, standard deviation plus lower and upper ranges.
Ethics approvals and informed consentEthical approvals were obtained from the Mulago Hospital Research Ethics Committee (MHREC 1922) and the Uganda National Council of Science and Technology (UNCST HS1042ES).Administrative approval (ADM.105/309/05) was obtained from Ministry of health.All participants gave written informed consents, while adult caregivers and health workers gave written informed assents.

Table 3 :
Incidence rate ratio (IRR) of adolescents screened for TB.

Table 4 :
Incidence rate ratio (IRR) for TB presumptive adolescents

Table 5 :
Incident rate ratio (IRR) of adolescents tested for TB